Antimicrobial properties of amyloid peptides

Bruce L. Kagan, Hyunbum Jang, Ricardo Capone, Fernando Teran Arce, Srinivasan Ramachandran, Ratnesh Lal, Ruth Nussinov

Research output: Contribution to journalReview articlepeer-review

145 Scopus citations

Abstract

More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids not only are toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function.

Original languageEnglish (US)
Pages (from-to)708-717
Number of pages10
JournalMolecular Pharmaceutics
Volume9
Issue number4
DOIs
StatePublished - Apr 2 2012
Externally publishedYes

Keywords

  • amyloid ion channels
  • antimicrobial activity
  • cytotoxicity
  • β-strand-turn-β-strand motif

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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